Objective To explore the effects of different intravenous immunoglobulin (IVIG) therapy on the prognosis of neonatal ABO hemolysis. Methods 68 children patients with ABO hemolysis were randomly divided into high-dose group (group A, 34 cases) and low-dose group (group B, 34 cases). Group A was given single high-dose IVIG+ routine treatment, and group B was given two-time low-dose IVIG+ routine treatment. The changes of serum total bilirubin (TBIL) level in the two groups were observed before and after treatment. The red blood cells (RBC), hematocrit (HCT), hemoglobin (Hb), and illumination time and hospital stay were compared between the two groups after 5 d of treatment. Results After 1, 3 and 5 d of treatment, the serum TBIL levels in the two groups were lower than those before treatment, and the level in group A was lower than that in group B (P<0.05). After 5 d of treatment, the levels of RBC, HCT and Hb in group A were higher than those in group B (P<0.05). The illumination time and hospital stay in group A were shorter than those in group B (P<0.05). Conclusion Single high-dose IVIG has good effects in the treatment of ABO hemolysis, and it can effectively improve the anemia symptoms of children patients, shorten the illumination time and hospital stay, and is beneficial to the outcome of disease.